Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer, heart disease and birth defects. Currently under investigation are genes involved in inherited breast and ovarian cancer. Studies are designed to better understand the function and genetics of the BRCA1 and BRCA2 genes. We have previously screened patients with familial breast and ovarian cancer for mutations in these genes. The biological function of the BRCA1 protein is currently unknown. This question is being addressed at the whole animal and biochemical level. We have purified a portion of the BRCA1 protein and used it to screen for other proteins that specifically interact with the BRCA1 protein. We have demonstrated that BRCA1 interacts with other proteins involved in chromatin remodeling and DNA repair including histone deactylase. We are currently assessing the role of this complex in tumor formation. We are also testing cell lines derived from BRCA1 and BRCA2 mutation carriers for alterations in their chromatin remodeling pathways. An increased understanding of these genes will lead to improved diagnostic procedures and possible preventative therapies. - BRCA1/2, breast cancer, genetics, Women's Health Research